A Nano “Immune‐Guide” Recruiting Lymphocytes and Modulating the Ratio of Macrophages from Different Origins to Enhance Cancer Immunotherapy

Abstract

Artificially modulating the type, density, and location of immune cells within the tumor microenvironment can suppress tumor growth and efficiently promote current immunotherapy. In this study, a magnetite nanoparticle‐based “immune‐guide” is developed by the functionalization of magnetite nanoparticles with hyaluronic acid (HA). HA, an extracellular matrix component, can target various CD44‐overexpressing tumors and mediate the adhesion and migration of multiple types of immune cells. Thus, HA‐functionalized magnetite nanoparticles (HA‐PDA@Fe3O4) can highly efficiently accumulate in breast cancer and penetrate deep into the tumor parenchyma. Consequently, high intratumoral concentration of HA, serving as a “guidepost,” can directly recruit lymphocytes and elicit more chemokine production through cascading amplification effects, turning the immune “cold” tumor into a “hot” one. More importantly, HA‐PDA@Fe3O4 can effectively remodel the diversity, origin, and activation of tumor‐associated macrophages by recruiting and activating infiltrating macrophages, while simultaneously reducing the M2‐maintained tissue‐resident macrophages. Thus, HA‐PDA@Fe3O4 synergistically improves T cell‐ and macrophage‐based immunotherapies as well as interferes with the formation of premetastatic niches in the lung. By redistributing the localization of HA in tumors by using magnetite nanoparticles, this study provides a unique strategy to modulate the tumor immune microenvironment and potentiate tumor immunotherapies by using biocompatible nanomaterials without any therapeutic drug.

Near-infrared II plasmonic porous cubic nanoshells for in vivo noninvasive SERS visualization of sub-millimeter microtumors

“…Significant CD44 overexpression on the cell membrane of 4T1 breast cancer cells has been previously confirmed and extensively employed for the development of targeting drug delivery systems 45,[49][50][51] . The effective tumor accumulation of NIR-II SERS probes may be attributed to the combination of the passive enhanced permeability and retention (EPR) effect and the active targeting of CD44 overexpressed on the 4T1 tumor cells 1,45,51,52 . We further examined the suitability of our NIR-II SERS probes for in vivo NIR-II SERS imaging of a tumor in a 4T1 tumor-bearing mouse.…”

Emerging Nanoparticle Strategies for Modulating Tumor-Associated Macrophage Polarization

“…In an animal model with human breast cancer MDA-MB-231, the hollow nanomedicine inhibited tumor development [ 94 ]. Hyaluronic acid (HA) was carried by various iron oxide nanoparticles to regulate macrophages to promote the polarization effect [ 95 , 96 , 97 ]. Of note, the clinical observation is in accordance with the story above, where the number of iron-containing TAMs in patients with non-small cell lung cancer is usually associated with tumor regression [ 98 ].…”

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy

“…The specific tumor extracellular Glu release accompanied by intracellular delivery of iron-based molecules and fluvastatin is necessary to effectively enhance Fenton reaction, and the sophisticated cancer nanomedicines developed for multiple delivery routes shed light on such on-demand delivery for a portfolio of antitumor agents. − In particular, the noninvasive pulmonary nanomedicine delivery system is emerging as a promising approach to elevate drug concentration in the lung and avoid systematic adverse effects, which have been successfully employed in the therapy of asthma, cystic fibrosis, pneumonia, and chronic obstructive pulmonary diseases. − Equipped with exquisite anatomical and cellular delivery specificity, inhaled nanomedicines such as chitosan nanoparticles, liposomes, and nanostructured lipid carriers (NLC) were expected to deposit in the respiratory tract and finally reach lung lesions. Among them, NLC was considered as an ideal pulmonary delivery nanocarrier with its high biocompatibility and excellent drug-loading capacity .…”